ArticleNature communications2023
Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Fisher Information Limits on Genetic Stability, Diversity, and Regulation.Bulletin of mathematical biology · 2026Article
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- An integrated analysis of MEN1 reveals its associations with clinical outcomes, cellular pathways, and the immune microenvironment.World journal of surgical oncology · 2026Article
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer.Cell reports. Medicine · 2025Article
- ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.Journal of molecular cell biology · 2025Article
- Systematic genetic perturbation reveals principles underpinning robustness of the epigenetic regulatory network.Nucleic acids research · 2025Article
- A narrative review of epigenetic marker in H3K27ac and its emerging potential as a therapeutic target in cancer.Epigenomics · 2025Review
- Progress report on multiple endocrine neoplasia type 1.Familial cancer · 2025Review
- Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.Nature biotechnology · 2024Article
- Generation of programmable splicing factors using RNA-binding proteins that activate exon inclusion.Nature biotechnology · 2024Article
- Crosstalk within and beyond the Polycomb repressive system.The Journal of cell biology · 2024Review
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
- Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.International journal of molecular sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Interplay between chromatin-associated complexes and modifications critically contribute to the partitioning of epigenome into stable and functionally distinct domains. Yet there is a lack of systematic identification of chromatin crosstalk mechanisms, limiting our understanding of the dynamic transition between chromatin states during development and disease. Here we perform co-dependency mapping of genes using CRISPR-Cas9-mediated fitness screens in pan-cancer cell lines to quantify gene-gene functional relationships. We identify 145 co-dependency modules and further define the molecular context underlying the essentiality of these modules by incorporating mutational, epigenome, gene expression and drug sensitivity profiles of cell lines. These analyses assign new protein complex composition and function, and predict new functional interactions, including an unexpected co-dependency between two transcriptionally counteracting chromatin complexes - polycomb repressive complex 2 (PRC2) and MLL-MEN1 complex. We show that PRC2-mediated H3K27 tri-methylation regulates the genome-wide distribution of MLL1 and MEN1. In lymphoma cells with EZH2 gain-of-function mutations, the re-localization of MLL-MEN1 complex drives oncogenic gene expression and results in a hypersensitivity to pharmacologic inhibition of MEN1. Together, our findings provide a resource for discovery of trans-regulatory interactions as mechanisms of chromatin regulation and potential targets of synthetic lethality.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.